Although the underlying mechanisms are not understood, the importance of the major histocompatibility complex in controlling immune responses and in determining susceptibility to some diseases has been well documented. We propose to investigate whether resistance and susceptibility to mouse mammary tumor viruses from various sources are associated with the H-2 complex in mice; to determine the number of genes involved; to map the gene or genes within this complex; and to study the immunologic basis for the differences among strains. This proposal represents a joint effort by two groups of investigators at different institutions, one group experienced in the genetic control of immune responses in mice (Jefferson Medical College, Philadelphia), the other involved in a multi-disciplinary effort to understand murine mammary tumorigenesis (Hahnemann Medical College & Hospital, Philadelphia). Because differences exist in the host range of mammary tumor viruses, graded dilutions of virus from five different sources will be tested for tumorigenesis in a number of congenic, recombinant, and hybrid strains. Viral antigen and nucleic acid in the inocula will be quantitated and measurement of viral replication in the hosts will be undertaken. The cellular and humoral responses of these mice will also be followed during the two-year observation period. Such studies may illuminate mechanisms of host-tumor interaction and serve as a model for human breast cancer.